Methamphetamine (MA) dependence frequently co-occurs with HIV infection and greatly increases the likelihood of poorer disease outcomes, in part due to high rates of antiretroviral (ARV) nonadherence, for which there are presently no reliably effective clinical interventions in HIV-infected MA users. Neurocognitive impairment is an important risk factor for non-adherence and is therefore a viable candidate for interventions that might improve adherence (and other health outcomes). One aspect of cognition that is affected in both HIV and MA, is particularly relevant to ARV adherence, and may be a prime target for intervention is prospective memory (PM), which is the ability to remember to perform an intended action at a specific point in the future (i.e., remembering to remember). HIV-associated deficits in PM are strongly and uniquely associated with declines in everyday functioning that greatly burden our healthcare systems, particularly ARV nonadherence, because individuals must remember to take their medications as prescribed. However, there are presently no empirically validated, theory-driven techniques to improve adherence-related cognitive functions such as PM in MA and HIV. One novel and potentially powerful approach to improving PM is self-generation, a process by which one must produce the material to be remembered. Considered within the framework of Einstein and McDaniel's Multi-Process Theory of PM, self-generation may bolster PM performance by enhancing the automatic nature of encoding, thereby decreasing demands on dysfunctional strategic (i.e., executive) aspects of encoding and cue monitoring that underlie PM impairment in MA/HIV individuals. Self-generation may therefore be a highly effective means of enhancing PM (and thus, perhaps adherence) in this high-risk population. The proposed dissertation research study seeks to: 1) evaluate the efficacy of self-generation on PM performance in MA/HIV adults on basic experimental, clinical laboratory, and naturalistic PM paradigms; 2) determine the neurocognitive moderators of self-generation on PM in MA/HIV; and 3) explore potential demographic (e.g., education), psychiatric (e.g., Major Depressive Disorder), HIV disease (e.g., nadir CD4 counts), and addiction (e.g., recency of MA use) correlates of the self-generation effect on PM in MA/HIV. These study aims will be evaluated in 55 well-characterized HIV+ MA users and 25 seronegative comparison subjects drawn from the UCSD HIV Neurobehavioral Research Program, who will complete a series of self-generation PM experiments in the laboratory and in a naturalistic setting. Results from this study are intended to directly inform te development of PM-based strategies to improve adherence in MA/HIV. Moreover, the training goals and activities outlined in this fellowship application aim to bolster the applicant's knowledge, skills, and experience in enhancing cognitive outcomes in addictions and neuroAIDS, in service of her long-term goals of an academic research career in the rehabilitation of cognitive and everyday functioning (e.g., non-adherence) deficits in persons living with HIV infection and addictions. PUBLIC HEALTH RELEVANCE: In spite of therapeutic advancements in managing the virologic aspects of HIV infection, HIV-associated neurocognitive disorders (HAND) persist and result in significant problems in everyday functioning, particularly medication nonadherence. Yet there are no empirically supported medical or psychological treatments to improve HAND. This training grant will evaluate the usefulness of a new neurorehabilitation technique for enhancing one particularly impactful aspect of HAND (i.e., prospective memory) in a high-risk population of HIV-infected methamphetamine users.